Simulation of the Impact of Statin Intolerance on the Need for Ezetimibe and/or Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor for Meeting Low-Density Lipoprotein Cholesterol Goals in a Population With Atherosclerotic Cardiovascular Disease

Am J Cardiol. 2019 Apr 15;123(8):1202-1207. doi: 10.1016/j.amjcard.2019.01.028. Epub 2019 Jan 25.

Abstract

In a population with atherosclerotic cardiovascular disease, previous research indicated that approximately 86% can achieve low-density lipoprotein cholesterol (LDL-C) of <70 mg/dL with oral lipid-lowering therapies (LLT) only, whereas 14% would require a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. We aim to estimate these values accounting for varying levels of statin intolerance. A simulation model described previously was used to estimate the utilization of LLT needed to achieve LDL-C <70 mg/dL via an intensification algorithm which maximized statins before adding ezetimibe or a PCSK9 inhibitor. The current analysis took into account varying background rates of statin intolerance. We defined statin intolerance as either partial (inability to tolerate high-intensity statin) or full (inability to tolerate any statin). With treatment intensification and 10% of patients having partial statin intolerance, the use of ezetimibe (± statin ± PCSK9 inhibitor) increased from 32.7% to 34.9%, and the need for a PCSK9 inhibitor (+ ezetimibe ± statin) increased from 14.0% to 15.5%. If, instead, 10% were fully statin intolerant, the use of ezetimibe (± statin ± PCSK9 inhibitor) increased from 32.7% to 38.5%, and the use of a PCSK9 inhibitor (+ ezetimibe ± statin) increased from 14.0% to 19.7%. In conclusion, in our simulation-based study, partial statin intolerance increased the need for nonstatins only modestly (by an absolute 2.2%), whereas having 10% of patients with full statin intolerance increased the need for PCSK9 inhibitors from 14% overall to approximately 20%.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Anticholesteremic Agents / therapeutic use
  • Atherosclerosis / blood
  • Atherosclerosis / drug therapy*
  • Atorvastatin / therapeutic use*
  • Cardiovascular Diseases
  • Cholesterol, LDL / blood*
  • Drug Therapy, Combination
  • Drug Tolerance*
  • Ezetimibe / therapeutic use*
  • Follow-Up Studies
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • PCSK9 Inhibitors*
  • Retrospective Studies

Substances

  • Anticholesteremic Agents
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • PCSK9 Inhibitors
  • Atorvastatin
  • PCSK9 protein, human
  • Ezetimibe